Anti-SARS-CoV-2 Activity and Cytotoxicity of Amaryllidaceae Alkaloids from Hymenocallis littoralis.

The Amaryllidaceae species are well-known as a rich source of bioactive compounds in nature. Although Hymenocallis littoralis has been studied for decades, its polar components were rarely explored. The current phytochemical investigation of Amaryllidaceae alkaloids from H. littoralis led to the identification of three previously undescribed compounds: O-demethyl-norlycoramine (1), (-)-2-epi-pseudolycorine (2) and (+)-2-epi-pseudolycorine (3), together with eight known compounds: 6α-hydroxyhippeastidine (4), 6ß-hydroxyhippeastidine (5), lycorine (6), 2-epi-lycorine (7), zephyranthine (8), ungeremine (9), pancratistatin (10) and 9-O-demethyl-7-O-methyllycorenine (11). Among the eight previously reported compounds, five were isolated from H. littoralis for the first time (compounds 4, 5, 7, 8, and 9). Compounds 1, 4, 5, 7, 8, and 11 exhibited weak anti-SARS-CoV-2 activity (EC50 = 40-77 µM) at non-cytotoxic concentrations. Assessment of cytotoxicity on the Vero-E6 cell line revealed lycorine and pancratistatin as cytotoxic substances with CC50 values of 1.2 µM and 0.13 µM, respectively. The preliminary structure-activity relationship for the lycorine-type alkaloids in this study was further investigated, and as a result ring C appears to play a crucial role in their anti-SARS-CoV-2 activity.

Antiplasmodial Oleanane Triterpenoids from Terminalia albida Root Bark.

Phytochemical investigation of the n-BuOH extract of the roots of Terminalia albida Sc. Elliot (Combretaceae) led to the isolation and identification of 10 oleanane triterpenoids (1-10), among which six new compounds, i.e., albidanoside A (2), albidic acid A (4), albidinolic acid (5), albidienic acid (8), albidolic acid (9), and albidiolic acid (10), and two triterpenoid aglycones, i.e., albidic acid B (6) and albidic acid C (7), were isolated here for the first time from a natural source, along with two known compounds. The structures of these constituents were established by means of 1D and 2D NMR spectroscopy and ESI mass spectrometry. The isolated compounds were evaluated for their antiplasmodial and antimicrobial activity against the chloroquine-resistant strain Plasmodium falciparum K1, Candida albicans, and Staphylococcus aureus. Compounds 1-4, 6, 7, and 8 showed moderate antiplasmodial activity with IC50 values between 5 and 15 µM. None of the tested compounds were active against C. albicans or S. aureus. These findings emphasize the potential of T. albida as a source for discovery of new antiplasmodial compounds.

Antiplasmodial activity of Mezoneuron benthamianum leaves and identification of its active constituents.

ETHNOPHARMACOLOGICAL RELEVANCE: Decoctions of the leaves of M. benthamianum Baill. are used by traditional healers in Guinea to treat malaria and this use was validated by a preliminary clinical assay. AIM OF THE STUDY: To evaluate the in vitro antiplasmodial activity and to identify active compounds from extracts of M. benthamianum leaves. MATERIAL AND METHODS: Antiplasmodial activity of extracts, fractions and pure compounds was evaluated in vitro against a chloroquine-sensitive strain of Plasmodium falciparum (3D7) using the measurement of the plasmodial lactate dehydrogenase activity. Selectivity of extracts and purified compounds for Plasmodium parasites was evaluated by using WST-1 test on HeLa human cells. Compounds were isolated using normal phase silica gel column chromatography and prepHPLC and their structures elucidated using extensive spectroscopic analysis. RESULTS: Hydroethanolic extracts (70% v/v) of M. benthamianum leaves showed a moderate in vitro activity against P. falciparum 3D7, with IC50 in the range 22.5 - 32.6µg/mL, depending on the batch; while a dark precipitate formed during ethanol evaporation showed higher activity (IC50 =6.5µg/mL). The fractionation was performed on this most active fraction and was followed by in vitro antiplasmodial assay. Active compounds (5, 7, 8) belong to several phytochemical classes, contributing together to the global antiplasmodial activity of the hydroethanolic extract against P. falciparum parasite. This study finally allowed the isolation of three diterpenes including two new compounds named Mezobenthamic acids A (1) and B (2) and neocaesalpin H (3), as well as quercetin (4), kaempferol (7), resveratrol (6), gallic acid (9) and its ethylester (5), ß-sitosterol glucoside (10) and 13b-hydroxy-pheophorbide a (8). CONCLUSION: This study gives some concrete evidence to support the ethnopharmacological use of Mezoneuron benthamianum leaves extract in the management of malaria. The active compounds can be further studied for their antiplasmodial potential, as well as their suitability to be used as quality markers for the standardization of this herbal drug from the Guinean traditional pharmacopeia.

In vitro antiprotozoal, antimicrobial and antitumor activity of Pavetta crassipes K. Schum leaf extracts.

AIM OF THE STUDY: To study the potential benefit of the traditional medicinal plant Pavetta crassipes K. Schum (Rubiaceae), which is widely distributed throughout West Africa, the methanol and dichloromethane extracts were isolated from the plant leaves to determine if they exhibited antiprotozoal, antibacterial, antifungal or antitumor activity in vitro. MATERIALS AND METHODS: The methanol and dichloromethane extracts and their specific fractions were obtained using bioassay-guided fractionation and investigated for antiproliferative activity in vitro in microorganisms (Staphylococcus aureus, Escherichia coli and Candida albicans), protozoans (Trypanosoma cruzi, Trypanosoma brucei, Leishmania infantum and Plasmodium falciparum), and cancer (U373, PC3, MXT and A549) and normal cell lines (NHDF and MRC-5). RESULTS: Most of the alkaloid fractions investigated exhibited antiproliferative activity in all the cancer cell lines, microorganisms and protozoans studied. CONCLUSIONS: The benefit of Pavetta crassipes as a traditional medicinal remedy was confirmed using antiprotozoal and cytotoxicity assays in vitro. These analyses revealed that the components present in the alkaloid extract of Pavetta crassipes are responsible for its antiprotozoal and cytotoxic efficacy.